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Multicenter Study
. 2023 Aug;9(8 Pt 1):1296-1306.
doi: 10.1016/j.jacep.2023.03.008. Epub 2023 May 24.

Genetics in Probands With Idiopathic Ventricular Fibrillation: A Multicenter Study

Luigi Pannone  1 , Anaïs Gauthey  1 , Giulio Conte  2 , Randy Osei  3 , Daniela Campanale  2 , Enrico Baldi  4 , Paola Berne  5 , Alessandro Vicentini  4 , Pasquale Vergara  1 , Antonio Sorgente  1 , Christine Rootwelt-Norberg  6 , Domenico Giovanni Della Rocca  1 , Cinzia Monaco  1 , Antonio Bisignani  1 , Vincenzo Miraglia  1 , Marcello Spolverini  4 , Gaetano Paparella  1 , Ingrid Overeinder  1 , Gezim Bala  1 , Alexandre Almorad  1 , Erwin Ströker  1 , Thomy de Ravel  7 , Argelia Medeiros-Domingo  8 , Juan Sieira  1 , Kristina H Haugaa  6 , Pedro Brugada  1 , Mark La Meir  9 , Angelo Auricchio  2 , Gian-Battista Chierchia  1 , Sonia Van Dooren  7 , Carlo de Asmundis  10
Affiliations
Free article
Multicenter Study

Genetics in Probands With Idiopathic Ventricular Fibrillation: A Multicenter Study

Luigi Pannone et al. JACC Clin Electrophysiol. 2023 Aug.
Free article

Abstract

Background: Different genes have been associated with idiopathic ventricular fibrillation (IVF); however, there are no studies correlating genotype with phenotype.

Objectives: The aim of this study was to define the genetic background of probands with IVF using large gene panel analysis and to correlate genetics with long-term clinical outcomes.

Methods: All consecutive probands with a diagnosis of IVF were included in a multicenter retrospective study. All patients had: 1) IVF diagnosis throughout the follow-up; and 2) genetic analysis with a broad gene panel. All genetic variants were classified as pathogenic/likely pathogenic (P+), variants of unknown significance (VUS) or no variants (NO-V), following current guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The primary endpoint was occurrence of ventricular arrhythmias (VA).

Results: Forty-five consecutive patients were included. A variant was found in 12 patients, 3 P+ and 9 VUS carriers. After a mean follow-up time of 105.0 months, there were no deaths and 16 patients (35.6%) experienced a VA. NO-V patients had higher VA free survival during the follow-up, compared with both VUS (72.7% vs 55.6%, log-rank P < 0.001) and P+ (72.7% vs 0%, log-rank P = 0.013). At Cox analysis, P+ or VUS carrier status was a predictor of VA occurrence.

Conclusions: In probands with IVF, undergoing genetic analysis with a broad panel, the diagnostic yield for P+ is 6.7%. P+ or VUS carrier status is a predictor of VA occurrence.

Keywords: genetics; idiopathic ventricular fibrillation; next-generation sequencing; sudden cardiac death.

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Conflict of interest statement

Funding Support and Author Disclosures This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Dr Osei is supported by the Bridge 2017: IGenCare: Integrated Personalised Medical Genomics Care Solution for Patients With Rare Genetic Diseases grant of Innoviris, Brussels. Dr Berne has received compensation for teaching purposes from Biotronik. Dr Bisignani is a consultant for Biotronik. Dr Miraglia has received an educational grant from the Enrico and Enrica Sovena Foundation. Dr Medeiros-Domingo is the founder and medical director of SwissDNAlysis. Dr La Meir is a consultant for Atricure. Dr Auricchio is a consultant for Abbott, Boston Scientific, Backbeat, Cairdac, Corvia, Medtronic, Microport CRM, Philips, XSpline; participates in clinical trials sponsored by Bayer AG, Boston Scientific, Medtronic, and Microport CRM. Dr Chierchia has received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. Dr de Asmundis has received research grants on behalf of the center from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, and Acutus; has received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Livanova, Boston Scientific, Atricure, Acutus Medical, Daiichi Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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